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Systemic analysis of transcriptome in cancer and precancerous lesion of the esophagus and stomach

食管胃癌及癌前病变转录组的系统分析

基本信息

批准号：
13470045
负责人：
YASUI Wataru
金额：
$ 9.09万
依托单位：
HIROSHIMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470045/
关键词：
Gastric cancer Esophageal cancer Precancerous lesion Gene expression Transcriptome SAGE Regenerating gene type IV γCOP 食堂癌

项目摘要

To understand the detailed molecular mechanism of development and progression of esophageal and gastric cancer, we examined global gene expression profile in two types of primary gastric cancer through serial analysis of gene expression (SAGE), and compared with over 120 SAGE libraries of other normal and tumor tissues in the database. We have identified at least 8 genes/tags highly expressed in poorly differentiated type gastric cancer. Among them, regenerating gene type IV (Reg IV) was highly expressed in gastric cancer but not in cancer of the esophagus, lung, breast, and liver by RT-PCR. Strong expression was confirmed in gastric cancer cells by in situ hybridization. Introduction of Reg IV gene into gastric cancer cell line revealed that Reg IV protein was secreted into culture media and stimulated cell growth. We have also analyzed the gene expression profiles of the primary gastric cancer and its metastatic tumor from the same patient. It was identified 3 genes/tags (γCOP, p21 and unknown tag) whose expression was markedly reduced or lost in metastatic tumor. γCOP is one of the seven subunits forming COPI coat complex and mediates transport between Golgi and the endoplasmic reticulum. After laser capture microdissection to enrich target cells, obvious reduction in γCOP expression was confirmed in metastatic tumors by RT-PCR. We are studying the expression of these genes in precancerous lesions of the esophagus and stomach. Unknown tags detected in this study must be candidate novel genes for stomach carcinogenesis. We identified several tags specifically expressed in scattered (scirrhous) type gastric cancer, called SESs. Reverse SAGE and 5'RACE method will clone novel genes which may participate in development and progression of esophago-gastric cancer and serve as therapeutic targets.

为深入了解食管癌和胃癌发生发展的分子机制，我们通过基因表达序列分析（SAGE）检测了两种原发性胃癌的基因表达谱，并与数据库中其他正常组织和肿瘤组织的120多个SAGE文库进行了比较。我们已经鉴定出至少8个基因/标签在低分化型胃癌中高表达。其中，再生基因IV型（Reg IV）在胃癌中高表达，而在食管癌、肺癌、乳腺癌和肝癌中不表达。原位杂交证实在胃癌细胞中有强表达。将Reg IV基因导入胃癌细胞系，发现Reg IV蛋白分泌到培养基中，刺激细胞生长。我们还分析了同一患者的原发性胃癌及其转移瘤的基因表达谱。发现3个基因/标签（γCOP、p21和未知标签）在转移性肿瘤中表达明显降低或缺失。γCOP是形成COPI包被复合物的七个亚基之一，并介导高尔基体与内质网之间的转运。经激光捕获显微解剖富集靶细胞后，RT-PCR证实转移性肿瘤中γ - cop表达明显降低。我们正在研究这些基因在食道和胃癌前病变中的表达。本研究中检测到的未知标签可能是胃癌发生的候选新基因。我们发现了几个在散在型胃癌（SESs）中特异性表达的标签。反向SAGE和5'RACE方法将克隆可能参与食管胃癌发生发展的新基因，并作为治疗靶点。